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Monoclonal Antibodies Specific for Rat Relaxin. V.Passive Immunization with Monoclonal Antibodies throughout the Second Half of Pregnancy Disrupts Development of the Mammary Apparatus and, Hence,Lactational Performance in Rats^*

Department of Physiology and Biophysics and College of Medicine University of Illinois at Urbana-Champaign Urbana, Illinois 61801;
the Department of Structural and Cellular Biology, University of South Alabama College of Medicine, Mobile, Alabama 36688

Address requests for reprints to: Dr. O. D. Sherwood, Department of Physiology and Biophysics, University of Illinois at Urbana-Champaign,524 Burrill Hall, 407 South Goodwin Avenue, Urbana,Illinois 61801-3704.

Abstract

There were two related objectives to this study. The first was to determine the influence of relaxin on development of the mammary apparatus (nipples and glands) during the second half of pregnancy. The second was to determine whether the relaxin-dependent development of the mammary apparatus was required for normal postpartum lactational performance. Both objectives were accomplished by neutralizing endogenous relaxin throughout the second half of pregnancy with a monoclonal antibody specific for rat relaxin (MCAl).

MCAl was administered iv to rats daily from days 12–22 of pregnancy. On day 22 the morphology of the mammary apparatus of MCAl-treated rats differed from that of controls; nipples were dramatically smaller, collagen fibers had significantly greater mean density and consistency, and elastin fibers had greater mean density, length, and interdigitation. In addition, the mean number of alveoli surrounding lactiferous ducts was significantly smaller in MCAl-treated rats than in controls. There were no differences between MCAl-treated rats and controls in the mean thickness of connective tissue surrounding ducts, the height or density of luminal cells lining lactiferous ducts, or the sizes of either adipocytes or arteries.

To examine lactational performance, MCAl-treated and control rats were cesarean sectioned between 2100–2400 h on day 22 of pregnancy and given foster pups born of untreated intact donors. Although both MCAl-treated rats and control rats exhibited a high incidence of maternal behavior after cesarean delivery, mean pup weight and incidence of live pups declined markedly during days 1–5 of fosterage in MCAl-treated rats compared to controls. Furthermore, unlike controls, there was no observable postpartum nipple development in MCAl-treated rats by day 5 of fosterage. Mammary glands obtained from MCAl-treated rats on day 5 of fosterage had markedly lower mean weight than controls.

This study demonstrates that passive immunization of endogenous relaxin throughout the second half of pregnancy disrupts development of the nipples and mammary glands in the rat. Moreover, it establishes that relaxin’s effects on the development of the mammary apparatus during pregnancy are essential for growth and survival of the young during lactation. (Endocrinology 129: 3034-3042,1991)

Footnotes

^* This work was supported by NIH Grant USPHS HD-08700.

Received May 13, 1991.

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